Vitamin D – historical note
This note was written by Frank Norman and was first published in the 2011/12 Mill Hill Essays.
In 1906 Frederic Gowland-Hopkins suggested that rickets might be caused by some deficiency of nutrition. A few years later in 1914 he proposed to the newly-established Medical Research Committee (the forerunner of the Medical Research Council) that this was a suitable subject for investigation. The Committee readily agreed and provided funds for Edward Mellanby to work on the nature and causation of rickets. In 1918, after a long series of carefully planned and controlled experiments, Mellanby presented clear evidence for a dietary deficiency as the essential cause of rickets, and that the factor which must be present in the diet was something present in animal fats, such as cod liver oil. In the following year the German researcher Kurt Huldschinsky further found that exposing children to radiation from a sun quartz lamp was effective in treating rickets. In 1922 the American nutritional biochemist Elmer McCollum demonstrated the presence of a fat-soluble substance in fish liver oil and called this new nutritional factor vitamin D.
Meanwhile, Henry Dale had invited Otto Rosenheim to come out of retirement to join NIMR as a visiting worker in order to develop his ideas on vitamin D. He became part of a multidisciplinary group led by physical chemist Robert Bourdillon and also including organic chemist Robert Callow and physiologist Hilda Bruce.This team showed in 1927 that a substance called ergosterol when irradiated formed a product that had activity like that of vitamin D. Rosenheim introduced Callow to sterol chemistry and Callow subsequently perfected a method of obtaining a purified crystalline form of vitamin D that proved to be a pivotal contribution.
The chemist Adolf Windaus, at the University of Göttingen, made a similar discovery about ergosterol at about the same time. He was a leading expert on sterols and indeed was awarded the Nobel Prize for Chemistry in 1928 for his work in the field. The British and German researchers collaborated, working in parallel. Another group in the Netherlands was also addressing the problem and within the space of a few months three separate active crystalline products had been isolated, in three different countries. However, it transpired that they were not pure substances. In 1931 Callow’s purification procedure produced crystalline vitamin D2, also known as ergocalciferol, and this was acknowledged by Windaus as the first pure, chemically identified form of the vitamin.
The sequence of events connected with the isolation of calciferol was described in detail in an account signed by six members of the NIMR team in 1932 and deposited in the NIMR library. This document also includes correspondence between Dale, Windaus and Bourdillon. It shows that competition between the two groups in London and Göttingen was intense, but that both information and materials were freely exchanged and good relations maintained.
This work on vitamin D, and that of other groups, made it possible to manufacture the vitamin in large quantities, allowing rickets to be eradicated.